These investigations will, as a primary purpose utilize hyperplastic-liver-nodules induced by the hepatic oncogens, ethionine and 2-fluorenylacetamide, as models for the study of essential molecular reactions, and associated cellular alterations, which occur during the process of hepatocarcinogenesis. These nodules, which persist and grow long after cessation of intake of the etiologic chemical carcinogen are composed of a markedly homogeneous cell population which is markedly similar irrespective of the inciting oncogen. A number of significant features (e.g. persistent growth, lack of either metastasis or cytological changes typical of malignancy, in vitro adaptation and preservation of hepatic parenchymal function, unusual glycogen metabolism, uniformity of cell structure and ultrastructure, unique populations of DNA, selective preservation of metabolites of the carcinogen, etc.) characterize these nodules and readily differentiate them from adjacent liver. Since some of these properties simulate changes seen in malignant hepatomas, and because loci cytologically identical to primary liver cancer are often seen in the midst of, and totally circumscribed by, these nodules, this lesion seems uniquely suited and highly relevant for exploitation in the elucidation of the mechanistic basis of critical events occuring during phases of the neoplastic process. This then is an additional purpose of these studies. The long range goal would be to objectively define, delineate, contrast and fully comprehend regulatory factors operative in normal liver, liver carcinoma typified by metastasis and insidious cell growth and hyperplastic-liver-nodules which, despite an augmented rate of cell replication, lack the capacity of either invasion or metastasis.